Region-specific laboratory reference intervals are important: A systematic review of the data from Africa

Abstract

Region-specific laboratory reference intervals (RIs) are important for clinical trials and these data are often sparse in priority areas for research, including Africa. We reviewed data on RIs from Africa to identify gaps in the literature with a systematic review of PubMed for RI studies from Africa published ≥2010. Search focus included clinical analytic chemistry, hematology, immunological parameters and RIs. Data from adults, adolescents, children, pregnant women, and the elderly were included. We excluded manuscripts reporting data from persons with conditions that might preclude clinical trial participation in studies enrolling healthy volunteers. Of 179 identified manuscripts, 80 were included in this review, covering 20 countries with the largest number of studies in Ethiopia (n = 23, 29%). Most studies considered healthy, nonpregnant adults (n = 55, 69%). Nine (11%) studies included pregnant women, 13 (16%) included adolescents and 22 (28%) included children. Recruitment, screening, enrollment procedures and definition of age strata varied across studies. The most common type of RIs reported were hematology (66, 83%); 14 studies (18%) included flow cytometry and/or T cell counts. Other common tests or panels included liver function assays (32, 40%), renal function assays (30, 38%), lipid chemistries (17, 21%) and serum electrolytes (17, 21%). The number of parameters characterized ranged from only one (three studies characterized either CD4+ counts, D-dimer, or hemoglobin), to as many as 40. Statistical methods for calculating RIs varied. 56 (70%) studies compared their results to international RI databases. Though most presented their data side-by-side with international data with little accompanying analysis, nearly all reported deviation from comparator RI data, sometimes with half or more of otherwise healthy participants having an “out of range” result. We found there is limited local RI data available in sub-Saharan Africa. Studies to fill this gap are warranted, including efforts to standardize statistical methods to derive RIs, methods to compare with other RIs, and improve representative participant selection.

Complete Blood Count Reference Intervals for Children Aged Less Than 1 to 12 Years in the Northern Region of Ghana

“…The RIs of the CBC parameters were lower than those of the URIT analyser, showing significant misclassification, with %OOR ranging from 2.1% to 100% when compared to the accompanying RIs from the manufacturer. Similar disproportions have been observed in some adult RI studies in Ghana [2,20] and other African countries [4], suggesting that the proportion of normal children whose CBC results are interpreted based on the manufacturer's RIs may be erroneously classified as having anaemia.…”

“…In most clinical situations, decisions regarding patient management, diagnosis, treatment progression, clinical trials, and legal issues are made using information from routinely requested medical laboratory tests [1]. This emphasises the need for reliable and accurate results with accompanying reference intervals (RIs) that are representative of a defined population to aid in better interpretation and appropriate clinical decisions [2][3][4][5]. Haematological RIs, which provide the basis for comparison and make meaning of test results, are influenced by sex, race/genetics, age, social lifestyle/environment, and the geographical origin of the population [6].…”

Variation in normative values of major clinical biochemistry analytes in healthy reproductive-age women in India

“…[ 6 ] The use of RIs outside the region of application could be misleading and may negatively affect clinical outcomes in patients. [ 7 ] Against the vast racial, ethnic, and environmental diversity, population-specific data generation is warranted. [ 8 ] The Clinical and Laboratory Standards Institute (CLSI) 2008 and the International Federation for Clinical Chemistry and Committee on RIs and Decision Limits provide guidelines for establishing population-specific RIs.…”

“…[ 11 12 13 ] Recent studies from Africa, Saudi Arabia, and Egypt reported that significant variation in biochemical parameters compared to standard reference ranges. [ 7 14 15 ] Data from previous studies from India were mainly limited to subregional/regional or hospital-based settings,[ 16 17 18 19 20 21 22 ] though fragmented, has also shown variation of biochemical analytes among Indian populations when compared to RIs corroborated in western cohorts. [ 20 21 22 23 24 25 26 ] Thus, studies on a nationally representative sample of apparently healthy Indian women of reproductive age are largely unavailable.…”